Download PDF

Clinical Trial Results:
A PHASE III, MULTICENTRE, DOUBLE BLIND, PROSPECTIVE, RANDOMISED, PLACEBO CONTROLLED STUDY ASSESSING THE EFFICACY AND SAFETY OF DYSPORT USED IN THE TREATMENT OF LOWER LIMB SPASTICITY IN CHILDREN WITH DYNAMIC EQUINUS FOOT DEFORMITY DUE TO CEREBRAL PALSY

Summary
EudraCT number	2009-017709-12
Trial protocol	FR PL
Global end of trial date	25 Jun 2014

Results information
Results version number	v2(current)
This version publication date	23 May 2025
First version publication date	26 Jul 2015
Other versions	v1 (removed from public view)
Version creation reason	Correction of full data set Data validation

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

Y-55-52120-141

ISRCTN number

US NCT number

NCT01249417

WHO universal trial number (UTN)

Sponsor organisation name

Ipsen Pharma SAS

Sponsor organisation address

65 Quai Georges Gorse,, Boulogne-Billancourt, France, 92100

Public contact

Medical Director, Ipsen Pharma SAS, clinical.trials@ipsen.com

Scientific contact

Medical Director, Ipsen Pharma SAS, clinical.trials@ipsen.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

09 Jun 2015

Is this the analysis of the primary completion data?

Yes

Primary completion date

25 Jun 2014

Global end of trial reached?

Yes

Global end of trial date

25 Jun 2014

Was the trial ended prematurely?

Main objective of the trial

The primary study objective will be to assess the efficacy of Dysport compared to placebo at Week 4 on the mean change from baseline in ankle joint hypertonicity in children with dynamic equinus foot deformity associated with cerebral palsy (CP).

Protection of trial subjects

This clinical study was designed and implemented and reported in accordance with the International Conference on Harmonisation Harmonized Tripartite Guidelines for Good Clinical Practice, with applicable local regulations (including European Directive 2001/20/EC, US Code of Federal Regulations Title 21, and Japanese Ministry of Health, Labor, and Welfare), and with the ethical principles laid down in the Declaration of Helsinki.

Background therapy

Evidence for comparator

Placebo

Actual start date of recruitment

05 Jul 2011

Long term follow-up planned

Yes

Long term follow-up rationale

Safety, Efficacy

Long term follow-up duration

7 Months

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Poland: 74

Country: Number of subjects enrolled

Chile: 16

Country: Number of subjects enrolled

Mexico: 39

Country: Number of subjects enrolled

Turkey: 62

Country: Number of subjects enrolled

United States: 50

Worldwide total number of subjects

241

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

218

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Each center that participated in the study was expected to randomize between 5 and 25 subjects. It was planned to have at least 2 participating centers per country.

Screening details

A total of 241 subjects were randomised to the study. The safety population included 239 subjects who were treated. Out of the 239 treated subjects, 4 subjects were excluded from the Intent-to-Treat (ITT) population because no modified ashworth scale (MAS) score was obtained at the baseline visit and/or at Week 4.

Period 1 title

Randomized population

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Dysport 10 U/Kg

Arm description

10 units per kilogram (U/Kg) per lower limb. Either 1 or both lower limbs can be treated. Total volume injected, 2 milliliter (ml) per leg. Botulinum type A toxin (Dysport®): Intramuscular (I.M.) (in the muscle) injection on Day 1 of a single treatment cycle.

Arm type

Experimental

Investigational medicinal product name

Botulinum type A toxin (Dysport)

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Dysport 10 U/Kg I.M. injection on either 1 or both lower limbs (2 ml per leg), single treatment.

Dysport 15 U/Kg

Arm description

15 U/Kg per lower limb. Either 1 or both lower limbs can be treated. Total volume injected, 2 ml per leg. Botulinum type A toxin (Dysport®): I.M. (in the muscle) injection on Day 1 of a single treatment cycle.

Arm type

Experimental

Investigational medicinal product name

Botulinum type A toxin (Dysport)

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Dysport 15 U/Kg I.M. injection on either 1 or both lower limbs (2 ml per leg), single treatment.

Placebo

Arm description

Total volume to be injected per lower limb - 2ml. Either 1 or both lower limbs can be treated. Placebo: I.M. injection on Day 1 of a single treatment cycle.

Arm type

Active comparator

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Placebo I.M. injection on either 1 or both lower limbs (2 ml per leg), single treatment.

Number of subjects in period 1	Dysport 10 U/Kg	Dysport 15 U/Kg	Placebo
Started	80	80	81
Treated	80	80	79
Completed	79	79	77
Not completed	1	1	4
No MAS score at baseline and/or Week 4	1	1	2
Study treatment not received	-	-	2

Period 2 title

Treatment phase - ITT population

Is this the baseline period?

Yes ^[1]

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Dysport 10 U/Kg

Arm description

10 U/Kg per lower limb. Either 1 or both lower limbs can be treated. Total volume injected, 2 ml per leg. Botulinum type A toxin (Dysport®): I.M. (in the muscle) injection on Day 1 of a single treatment cycle.

Arm type

Experimental

Investigational medicinal product name

Botulinum type A toxin (Dysport)

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Dysport 10 U/Kg I.M. injection on either 1 or both lower limbs (2 ml per leg), single treatment.

Dysport 15 U/Kg

Arm description

Arm type

Experimental

Investigational medicinal product name

Botulinum type A toxin (Dysport)

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Dysport 15 U/Kg I.M. injection on either 1 or both lower limbs (2 ml per leg), single treatment.

Placebo

Arm description

Total volume to be injected per lower limb - 2 ml. Either 1 or both lower limbs can be treated. Placebo: I.M. injection on Day 1 of a single treatment cycle.

Arm type

Active comparator

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Placebo I.M. injection on either 1 or both lower limbs (2 ml per leg), single treatment.

Notes
[1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
Justification: Baseline characteristic values were based on the ITT population, defined as all randomized subjects who received at least 1 injection of study treatment and who had a MAS score in the GSC assessed both at baseline and at Week 4.

Number of subjects in period 2 ^[2]	Dysport 10 U/Kg	Dysport 15 U/Kg	Placebo
Started	79	79	77
Completed	78	75	73
Not completed	1	4	4
Consent withdrawn by subject	1	3	1
Adverse event, non-fatal	-	-	1
Not specified	-	-	1
Lost to follow-up	-	1	1

Notes
[2] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: Only subjects who completed the Randomized phase were entered to Treatment phase of the study.

Baseline characteristics

Top of page

Reporting group title

Dysport 10 U/Kg

Reporting group description

Reporting group title

Dysport 15 U/Kg

Reporting group description

Reporting group title

Placebo

Reporting group description

Total volume to be injected per lower limb - 2 ml. Either 1 or both lower limbs can be treated. Placebo: I.M. injection on Day 1 of a single treatment cycle.

Reporting group values	Dysport 10 U/Kg	Dysport 15 U/Kg	Placebo	Total
Number of subjects	79	79	77	235
Age categorical
Units: Subjects
Children (2-9 years)	67	67	65	199
Children (10-17 years)	12	12	12	36
Age continuous
Units: years
arithmetic mean (standard deviation)	6 ( 3.3 )	5.7 ( 3.2 )	5.9 ( 3.5 )	-
Gender categorical
Units: Subjects
Female	45	48	48	141
Male	34	31	29	94
Race
Units: Subjects
Black/African American	2	0	5	7
Caucasian/White	57	60	55	172
American Indian/Alaskan Native	1	0	0	1
Multiple	19	19	17	55
Ethnicity
Units: Subjects
Hispanic/Latino	21	21	20	62
Not Hispanic/Latino	58	58	57	173
Botulinum toxin Status
Units: Subjects
Naive	40	41	41	122
Non-naive	39	38	36	113
Number of legs being treated
Units: Subjects
1 Leg injected	42	50	47	139
2 Leg injected	37	29	30	96
GMFCS Level
Subjects were staged according to the following Gross Motor Function Classification System (GMFCS) criteria: level 1 (walks without limitations [best outcome]), level 2 (walks with limitations) and level 3 (walks using a hand held mobility device [worst outcome]). Only subjects classified as GMFCS levels 1 to 3 were eligible for entry into the study.
Units: Subjects
GMFCS level 1	46	45	40	131
GMFCS level 2	24	24	30	78
GMFCS level 3	9	10	7	26
Height
Units: centimeter
arithmetic mean (standard deviation)	117.1 ( 20.7 )	111.6 ( 18.5 )	114.6 ( 19.7 )	-
Weight
Units: kg
arithmetic mean (standard deviation)	23.1 ( 13.4 )	21.1 ( 10.7 )	22.6 ( 11.9 )	-
Body Mass Index (BMI)
Units: kg/meter square
arithmetic mean (standard deviation)	15.8 ( 2.9 )	16.1 ( 2.7 )	16.2 ( 2.7 )	-
MAS score
The MAS is a 6-point scale which measures the intensity of muscle tone by measuring the resistance of the muscle to passive lengthening or stretching. The Investigator graded muscle tone in the gastrocnemius-soleus complex (GSC) from 0 (no increase in tone) to 4 (affected parts rigid in flexion or extension).
Units: Units on scale
arithmetic mean (standard deviation)	3.1 ( 0.3 )	3.1 ( 0.3 )	3.2 ( 0.4 )	-

End points

Top of page

Reporting group title

Dysport 10 U/Kg

Reporting group description

Reporting group title

Dysport 15 U/Kg

Reporting group description

Reporting group title

Placebo

Reporting group description

Total volume to be injected per lower limb - 2ml. Either 1 or both lower limbs can be treated. Placebo: I.M. injection on Day 1 of a single treatment cycle.

Reporting group title

Dysport 10 U/Kg

Reporting group description

Reporting group title

Dysport 15 U/Kg

Reporting group description

Reporting group title

Placebo

Reporting group description

Total volume to be injected per lower limb - 2 ml. Either 1 or both lower limbs can be treated. Placebo: I.M. injection on Day 1 of a single treatment cycle.

Primary: Change in MAS Score in the Gastrocnemius-soleus Complex (GSC) at the Ankle Joint of the (Most) Affected Lower Limb

Top of page

End point title

Change in MAS Score in the Gastrocnemius-soleus Complex (GSC) at the Ankle Joint of the (Most) Affected Lower Limb

End point description

The MAS is a 6-point scale which measures the intensity of muscle tone by measuring the resistance of the muscle to passive lengthening or stretching. Investigator will grade muscle tone in the GSC from 0 (no increase in tone) to 4 (affected parts rigid in flexion or extension). ITT population, defined as all randomized subjects who received at least 1 injection of study treatment and who had a MAS score in the GSC assessed both at baseline and at Week 4.

End point type

Primary

End point timeframe

Change from baseline to Week 4

End point values	Dysport 10 U/Kg	Dysport 15 U/Kg	Placebo
Number of subjects analysed	79	79	77
Units: Units on a scale
least squares mean (confidence interval 95%)	-0.86 (-1.07 to -0.65)	-0.97 (-1.18 to -0.76)	-0.48 (-0.69 to -0.27)

Dysport 10 U/kg/leg compared to Placebo

Statistical analysis description

MAS: Dysport 10 U/kg/leg compared to Placebo at Week 4. Least square (LS) means for each treatment group and treatment comparisons, as well as the p-values were obtained from an analysis of covariance (ANCOVA) on the change from baseline with treatment, baseline MAS score, age range at baseline, Botulinum toxin status at baseline and center as covariates.

Comparison groups

Dysport 10 U/Kg v Placebo

Number of subjects included in analysis

156

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0029

Method

ANCOVA

Parameter type

Difference in LS means

Point estimate

-0.38

Confidence interval

level

95%

sides

2-sided

lower limit

-0.64

upper limit

-0.13

Dysport 15 U/kg/leg compared to Placebo

Statistical analysis description

MAS: Dysport compared to placebo at Week 4. LS means for each treatment group and treatment comparisons, as well as the p-values were obtained from an ANCOVA on the change from baseline with treatment, baseline MAS score, age range at baseline, Botulinum toxin status at baseline and center as covariates.

Comparison groups

Placebo v Dysport 15 U/Kg

Number of subjects included in analysis

156

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0002

Method

ANCOVA

Parameter type

Difference in LS means

Point estimate

-0.49

Confidence interval

level

95%

sides

2-sided

lower limit

-0.75

upper limit

-0.23

Secondary: Physician’s Global Assessment (PGA) of the Treatment Response

Top of page

End point title

Physician’s Global Assessment (PGA) of the Treatment Response

End point description

PGA Scale of the Treatment Response: Global assessment of treatment response assessed by asking the Investigator the following question: "how would you rate the response to treatment in the subject's lower limb(s) since the last injection?" Answers will be made on a 9 point rating scale (-4: markedly worse, -3: much worse, -2: worse, -1: slightly worse, 0: no change, +1: slightly improved, +2: improved, +3: much improved, +4: markedly improved). ITT population, defined as all randomized subjects who received at least 1 injection of study treatment and who had a MAS score in the GSC assessed both at baseline and at Week 4.

End point type

Secondary

End point timeframe

Week 4

End point values	Dysport 10 U/Kg	Dysport 15 U/Kg	Placebo
Number of subjects analysed	79	79	77
Units: Units on a scale
least squares mean (confidence interval 95%)	1.54 (1.28 to 1.81)	1.5 (1.23 to 1.77)	0.73 (0.46 to 0.99)

Dysport 10 U/kg/leg compared to Placebo

Statistical analysis description

PGA: Dysport 10 U/kg/leg compared to placebo at Week 4. LS means for each treatment group and treatment comparisons, as well as the p-values were obtained from an analysis of variance (ANOVA) on the visit value with treatment, age range at baseline, Botulinum toxin status at baseline and center as covariates.

Comparison groups

Placebo v Dysport 10 U/Kg

Number of subjects included in analysis

156

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANOVA

Parameter type

Difference in LS means

Point estimate

0.82

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

1.14

Dysport 15 U/kg/leg compared to Placebo

Statistical analysis description

PGA: Dysport 15 U/kg/leg compared to placebo at Week 4. LS means for each treatment group and treatment comparisons, as well as the p-values were obtained from an ANOVA on the visit value with treatment, age range at baseline, Botulinum toxin status at baseline and center as covariates.

Comparison groups

Placebo v Dysport 15 U/Kg

Number of subjects included in analysis

156

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANOVA

Parameter type

Difference in LS means

Point estimate

0.77

Confidence interval

level

95%

sides

2-sided

lower limit

0.45

upper limit

1.1

Secondary: Goal Attainment Scale (GAS) Score

Top of page

End point title

Goal Attainment Scale (GAS) Score

End point description

GAS is a functional scale used to measure progress towards individual therapy goals. Individual goals defined for each subject by the physician, and the child's parents (caregiver) where applicable, prior to treatment. Post-baseline, the GAS for each goal rated using a defined scale (-2: Much less than expected outcome, -1: somewhat less than expected outcome, 0: expected outcome, 1: somewhat more than expected outcome, and 2: Much more than expected outcome). ITT population, defined as all randomized subjects who received at least 1 injection of study treatment and who had a MAS score in the GSC assessed both at baseline and at Week 4.

End point type

Secondary

End point timeframe

Week 4

End point values	Dysport 10 U/Kg	Dysport 15 U/Kg	Placebo
Number of subjects analysed	79	79	77
Units: Units on a scale
least squares mean (confidence interval 95%)	51.53 (49.05 to 54.01)	50.86 (48.36 to 53.36)	46.21 (43.7 to 48.72)

Dysport 10 U/kg/leg compared to Placebo

Statistical analysis description

GAS: Dysport 10 U/kg/leg compared to Placebo. LS means for each treatment group and treatment comparisons, as well as the p-values were obtained from an ANOVA on the visit value with treatment, age range at baseline, Botulinum toxin status at baseline and center as covariates.

Comparison groups

Dysport 10 U/Kg v Placebo

Number of subjects included in analysis

156

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0006

Method

ANOVA

Parameter type

Difference in LS means

Point estimate

5.32

Confidence interval

level

95%

sides

2-sided

lower limit

2.31

upper limit

8.32

Dysport 15 U/kg/leg compared to Placebo

Statistical analysis description

GAS: Dysport 15 U/kg/leg compared to Placebo. LS means for each treatment group and treatment comparisons, as well as the p-values were obtained from an ANOVA on the visit value with treatment, age range at baseline, Botulinum toxin status at baseline and center as covariates.

Comparison groups

Placebo v Dysport 15 U/Kg

Number of subjects included in analysis

156

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0031

Method

ANOVA

Parameter type

Difference in LS means

Point estimate

4.65

Confidence interval

level

95%

sides

2-sided

lower limit

1.59

upper limit

7.71

Adverse events

Top of page

Timeframe for reporting adverse events

Up to Week 28 of follow-up

Adverse event reporting additional description

The safety population, defined as all randomized subjects who received at least 1 injection of study treatment, was used for the analysis of adverse events (AEs).

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

17.0

Reporting group title

Dysport 10 U/Kg

Reporting group description

Dysport 10 U/Kg I.M. injection on either 1 or both lower limbs (2 ml per leg), single treatment.

Reporting group title

Dysport 15 U/Kg

Reporting group description

Dysport 15 U/Kg I.M. injection on either 1 or both lower limbs (2 ml per leg), single treatment.

Reporting group title

Placebo

Reporting group description

Placebo I.M. injection on either 1 or both lower limbs (2 ml per leg), single treatment.

Serious adverse events	Dysport 10 U/Kg	Dysport 15 U/Kg	Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 80 (1.25%)	0 / 80 (0.00%)	4 / 79 (5.06%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events	0	0	0
Injury, poisoning and procedural complications
Head injury
subjects affected / exposed	0 / 80 (0.00%)	0 / 80 (0.00%)	1 / 79 (1.27%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Upper limb fracture
subjects affected / exposed	0 / 80 (0.00%)	0 / 80 (0.00%)	1 / 79 (1.27%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Adenoidal hypertrophy
subjects affected / exposed	1 / 80 (1.25%)	0 / 80 (0.00%)	0 / 79 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Gastroenteritis
subjects affected / exposed	0 / 80 (0.00%)	0 / 80 (0.00%)	1 / 79 (1.27%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 80 (0.00%)	0 / 80 (0.00%)	1 / 79 (1.27%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Rotavirus infection
subjects affected / exposed	0 / 80 (0.00%)	0 / 80 (0.00%)	1 / 79 (1.27%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 2%

Non-serious adverse events	Dysport 10 U/Kg	Dysport 15 U/Kg	Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	51 / 80 (63.75%)	51 / 80 (63.75%)	42 / 79 (53.16%)
Injury, poisoning and procedural complications
Excoriation
subjects affected / exposed	2 / 80 (2.50%)	0 / 80 (0.00%)	0 / 79 (0.00%)
occurrences all number	2	0	0
Fall
subjects affected / exposed	1 / 80 (1.25%)	0 / 80 (0.00%)	2 / 79 (2.53%)
occurrences all number	1	0	2
Nervous system disorders
Epilepsy
subjects affected / exposed	2 / 80 (2.50%)	3 / 80 (3.75%)	0 / 79 (0.00%)
occurrences all number	3	4	0
Headache
subjects affected / exposed	0 / 80 (0.00%)	2 / 80 (2.50%)	1 / 79 (1.27%)
occurrences all number	0	3	1
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	6 / 80 (7.50%)	8 / 80 (10.00%)	4 / 79 (5.06%)
occurrences all number	7	8	4
Gastrointestinal disorders
Vomiting
subjects affected / exposed	3 / 80 (3.75%)	4 / 80 (5.00%)	4 / 79 (5.06%)
occurrences all number	3	5	4
Diarrhoea
subjects affected / exposed	2 / 80 (2.50%)	2 / 80 (2.50%)	1 / 79 (1.27%)
occurrences all number	2	2	1
Nausea
subjects affected / exposed	2 / 80 (2.50%)	1 / 80 (1.25%)	1 / 79 (1.27%)
occurrences all number	3	3	2
Abdominal pain upper
subjects affected / exposed	1 / 80 (1.25%)	0 / 80 (0.00%)	2 / 79 (2.53%)
occurrences all number	1	0	2
Abdominal pain
subjects affected / exposed	0 / 80 (0.00%)	0 / 80 (0.00%)	2 / 79 (2.53%)
occurrences all number	0	0	2
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	8 / 80 (10.00%)	6 / 80 (7.50%)	5 / 79 (6.33%)
occurrences all number	10	6	5
Oropharyngeal pain
subjects affected / exposed	1 / 80 (1.25%)	2 / 80 (2.50%)	0 / 79 (0.00%)
occurrences all number	1	2	0
Rhinorrhoea
subjects affected / exposed	1 / 80 (1.25%)	0 / 80 (0.00%)	2 / 79 (2.53%)
occurrences all number	1	0	2
Musculoskeletal and connective tissue disorders
Pain in extremity
subjects affected / exposed	2 / 80 (2.50%)	3 / 80 (3.75%)	4 / 79 (5.06%)
occurrences all number	2	3	4
Muscular weakness
subjects affected / exposed	2 / 80 (2.50%)	0 / 80 (0.00%)	1 / 79 (1.27%)
occurrences all number	2	0	1
Infections and infestations
Upper respiratory tract infection
subjects affected / exposed	6 / 80 (7.50%)	13 / 80 (16.25%)	10 / 79 (12.66%)
occurrences all number	8	15	11
Nasopharyngitis
subjects affected / exposed	10 / 80 (12.50%)	9 / 80 (11.25%)	4 / 79 (5.06%)
occurrences all number	13	10	8
Influenza
subjects affected / exposed	5 / 80 (6.25%)	6 / 80 (7.50%)	6 / 79 (7.59%)
occurrences all number	6	9	7
Bronchitis
subjects affected / exposed	3 / 80 (3.75%)	2 / 80 (2.50%)	2 / 79 (2.53%)
occurrences all number	4	2	2
Gastroenteritis viral
subjects affected / exposed	1 / 80 (1.25%)	2 / 80 (2.50%)	0 / 79 (0.00%)
occurrences all number	1	2	0
Ear infection
subjects affected / exposed	0 / 80 (0.00%)	2 / 80 (2.50%)	2 / 79 (2.53%)
occurrences all number	0	4	2
Upper respiratory tract infection bacterial
subjects affected / exposed	0 / 80 (0.00%)	2 / 80 (2.50%)	0 / 79 (0.00%)
occurrences all number	0	2	0
Pharyngitis
subjects affected / exposed	6 / 80 (7.50%)	1 / 80 (1.25%)	3 / 79 (3.80%)
occurrences all number	7	1	3
Rhinitis
subjects affected / exposed	3 / 80 (3.75%)	1 / 80 (1.25%)	3 / 79 (3.80%)
occurrences all number	3	1	3
Urinary tract infection
subjects affected / exposed	2 / 80 (2.50%)	1 / 80 (1.25%)	3 / 79 (3.80%)
occurrences all number	2	1	3
Respiratory tract infection viral
subjects affected / exposed	2 / 80 (2.50%)	1 / 80 (1.25%)	0 / 79 (0.00%)
occurrences all number	2	1	0
Viral infection
subjects affected / exposed	1 / 80 (1.25%)	1 / 80 (1.25%)	4 / 79 (5.06%)
occurrences all number	1	2	5
Varicella
subjects affected / exposed	4 / 80 (5.00%)	0 / 80 (0.00%)	1 / 79 (1.27%)
occurrences all number	4	0	1

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

07 Mar 2011

Amendment 1: • The GAS was changed from a 7-point scale to the validated 5-point scale. • Question 8 was omitted from the OGS, as central assessors were to evaluate and score each video in an independent manner and would not have the baseline videos for comparison to score Question 8 which assesses change from baseline. • The injection technique was modified to add the use of ultrasound as a complimentary muscle localisation method. • Clarification was added to the study rationale in response to French Central Ethics Committee's request. • A new contact number was added due to change of office reception number.

12 Jul 2011

Amendment 2: • The statistical methodology for the primary efficacy analysis was modified from a Hochberg procedure to a hierarchical testing procedure following feedback from the Food and Drug Administration. • Statistical sections were updated to ensure consistency between the Dysport protocols. • Written informed consent details were modified to clarify that either one or both parent(s)/guardian(s) would sign the informed consent form according to local legislation.

12 Jul 2012

Amendment 3: • The pharmacovigilance/emergency contact details for the USA and Latin America were updated. • Exclusion criterion 3 was modified to clarify the terminology for the exclusion of subjects based on the assessment of fixed myocontracture. • Exclusion criterion 7 was modified to clarify the exclusion of subjects with a need for surgery due to spasticity. • Exclusion criterion 7 was modified to clarify the exclusion of subjects with previous injection of alcohol or phenol. • Ipsen Pharma was replaced by Kymos Pharma as the central laboratory used for processing antibody samples. • The wording of Section 9.5 was amended to clarify the meaning and take into account all possibilities regarding used and unused treatments and empty boxes for destruction. • References to Sponsor’s Clinical Development Data Sciences Department were amended to Statistics Department.

25 Jul 2013

Amendment 4: • The 3-step hierarchical testing procedure was replaced by a 4-step hierarchical testing procedure in the section: Statistical Methodology for the Efficacy Analysis in View of Registration in the USA, as agreed upon with the Food and Drug Administration. • As a result of the agreement upon a 4-step hierarchical testing procedure, the sample size to demonstrate a statistically significant treatment effect on the mean Physician’s Global Assessment score was recalculated. • The pharmacovigilance/emergency contact details for the USA and Latin America were updated.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Clinical trials

Clinical Trial Results:
A PHASE III, MULTICENTRE, DOUBLE BLIND, PROSPECTIVE, RANDOMISED, PLACEBO CONTROLLED STUDY ASSESSING THE EFFICACY AND SAFETY OF DYSPORT USED IN THE TREATMENT OF LOWER LIMB SPASTICITY IN CHILDREN WITH DYNAMIC EQUINUS FOOT DEFORMITY DUE TO CEREBRAL PALSY

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change in MAS Score in the Gastrocnemius-soleus Complex (GSC) at the Ankle Joint of the (Most) Affected Lower Limb

Primary: Change in MAS Score in the Gastrocnemius-soleus Complex (GSC) at the Ankle Joint of the (Most) Affected Lower Limb

Secondary: Physician’s Global Assessment (PGA) of the Treatment Response

Secondary: Physician’s Global Assessment (PGA) of the Treatment Response

Secondary: Goal Attainment Scale (GAS) Score

Secondary: Goal Attainment Scale (GAS) Score

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A PHASE III, MULTICENTRE, DOUBLE BLIND, PROSPECTIVE, RANDOMISED, PLACEBO CONTROLLED STUDY ASSESSING THE EFFICACY AND SAFETY OF DYSPORT USED IN THE TREATMENT OF LOWER LIMB SPASTICITY IN CHILDREN WITH DYNAMIC EQUINUS FOOT DEFORMITY DUE TO CEREBRAL PALSY

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change in MAS Score in the Gastrocnemius-soleus Complex (GSC) at the Ankle Joint of the (Most) Affected Lower Limb

Primary: Change in MAS Score in the Gastrocnemius-soleus Complex (GSC) at the Ankle Joint of the (Most) Affected Lower Limb

Secondary: Physician’s Global Assessment (PGA) of the Treatment Response

Secondary: Physician’s Global Assessment (PGA) of the Treatment Response

Secondary: Goal Attainment Scale (GAS) Score

Secondary: Goal Attainment Scale (GAS) Score

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A PHASE III, MULTICENTRE, DOUBLE BLIND, PROSPECTIVE, RANDOMISED, PLACEBO CONTROLLED STUDY ASSESSING THE EFFICACY AND SAFETY OF DYSPORT USED IN THE TREATMENT OF LOWER LIMB SPASTICITY IN CHILDREN WITH DYNAMIC EQUINUS FOOT DEFORMITY DUE TO CEREBRAL PALSY